Harnessing HPV Virus-like\nNanoparticles for Efficient\nCircular RNA Delivery

Circular RNA (circRNA) has emerged\nas a promising class of therapeutics\nand mRNA vaccines. While possessing greater stability and functionality\nakin to linear mRNA, circRNA still necessitates an efficient and adaptable\ndelivery system to surmount the primary challenge of cellular uptake\nand membrane penetration. Inspired by the high invasiveness of the\nvirus, in this study, the virus-like nanoparticles (VLNPs) of human\npapillomavirus (HPV) have been constructed as robust carriers for\ncircRNA encapsulation and transfer through their coassembly monitoring.\nNotably, the functionalization of a transmembrane peptide (L17E) on\nthe outer surface of VLNPs has led to the development of a more efficient\nnanocarrier, which has significantly enhanced both the transmembrane\ndelivery and endosomal escape of circRNA. Validation studies employing\nVLNPs-L17E-packaged circRNA across various cell types have demonstrated\nnotable improvements in target protein expression, ranging from 1.48-\nto 2.04-fold. These findings underscore the potential of HPV-VLNPs-L17E\nas a carrier for circRNA delivery, offering promising prospects for\nRNA therapy applications in the future.